Tauriello, Daniele V. F.Sancho, ElenaByrom, DanielSánchez Zarzalejo, CarolinaSalvany, MariaHenriques, AnaPalomo Ponce, SergioSevillano, MartaHernando Momblona, XavierMatarin, Joan A.Ramos, IsraelRuano, IrenePrats, NeusBatlle, EduardRiera i Escalé, Antoni2024-11-262024-11-262024-12-012575-9108https://hdl.handle.net/2445/216759Blockade of the TGFβ signaling pathway has emerged from preclinical studies as a potential treatment to enhance the efficacy of immune checkpoint inhibition in advanced colorectal cancer (CRC) and several other types of cancer. However, clinical translation of first-generation inhibitors has shown little success. Here, we report the synthesis and characterization of HYL001, a potent inhibitor of TGFβ receptor 1 (ALK5), that is approximately 9 times more efficacious than the structurally related compound galunisertib, while maintaining a favorable safety profile. HYL001 in combination with immune checkpoint blockade (anti-PD1) eradicates liver metastases generated in mice by microsatellite stable, aggressive colorectal cancer tumors at doses where galunisertib is ineffective.16 p.application/pdfengcc-by (c) Tauriello, Daniele V. F., et al., 2024http://creativecommons.org/licenses/by/3.0/es/CàncerAnatomiaMetàstasiCancerAnatomyMetastasisinfo:eu-repo/semantics/article7520042024-11-26info:eu-repo/semantics/openAccess6694534